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Proenkephalin predicts kidney function and major adverse kidney events in CKD
Marleen Würfel1, Luise Pirlich1, Ekaterine Baratashvili1
1Department of Medicine III, Division of Endocrinology, Nephrology and Rheumatology, University of Leipzig, Leipzig, Germany.
Summary
Proenkephalin (PENK) levels are inversely linked to kidney function and predict major adverse renal events in chronic kidney disease (CKD) patients. Higher PENK indicates increased risk for kidney failure and adverse outcomes.
Area of Science:
- Neuropeptide and cardiovascular research
- Renal function and disease markers
- Biomarker discovery in chronic kidney disease (CKD)
Background:
- Endogenous opioid proenkephalin (PENK) is a known risk marker for acute cardiovascular diseases and acute kidney injury (AKI).
- Limited understanding exists regarding PENK regulation, its association with cardiometabolic markers, and its prognostic significance in chronic kidney disease (CKD) patients.
Purpose of the Study:
- To investigate the association between serum PENK levels and renal function markers in large cohorts.
- To explore the relationship between PENK and cardiometabolic markers.
- To determine the prognostic value of circulating PENK levels for adverse renal outcomes in CKD patients.
Main Methods:
- Cross-sectional analysis of PENK serum levels against renal and cardiometabolic markers in 4,722 participants across three cohorts (Leipzig-CKD, LIFE-Adult, Sorbs).
- Longitudinal analysis in the Leipzig-CKD cohort to assess PENK's association with a composite 4-point major adverse renal events (4P-MARE) endpoint over 8.7 years.
- Multivariable regression and Cox regression models were employed to identify independent predictors and prognostic value.
Main Results:
- PENK levels showed a strong inverse correlation with markers of renal function, including estimated glomerular filtration rate (eGFR), creatinine, and urinary albumin creatinine ratio (uACR).
- eGFR was identified as the strongest independent inverse predictor of circulating PENK levels.
- Baseline PENK levels significantly predicted an increased risk of 4P-MARE, with each doubling associated with over a two-fold increase in risk, independent of other clinical and metabolic variables.
Conclusions:
- Circulating PENK levels are independently and inversely associated with renal function in cross-sectional analyses.
- Baseline PENK levels serve as a significant predictor of major adverse renal events in patients.
- PENK provides added independent prognostic value for identifying patients at risk for adverse renal outcomes.
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